5-lipoxygenase: underappreciated role of a pro-inflammatory enzyme in tumourigenesis

Frontiers in Pharmacology

Jessica eRoos¹  Julia eMetzner¹  Svenja Dorothea Steinbrink¹  Thorsten Jürgen Maier¹  Dieter eSteinhilber¹  Astrid Stefanie Fischer¹  Martin eRuthardt¹ 

[1] Goethe University Frankfurt;

关键词: Apoptosis;    Cell Proliferation;    off-target effect;    Cytotoxicity;    Pancreatic Cancer;    leukotriene;   

DOI  :  10.3389/fphar.2010.00143

来源: DOAJ

【 摘 要 】

Leukotrienes (LTs) constitute a group of bioactive lipids generated by the 5-lipoxygenase (5-LO) pathway. An increasing body of evidence supports an acute role for 5-LO products already during the earliest stages of pancreatic, prostate and colorectal carcinogenesis. First, several independent studies documented an overexpression of 5-LO in primary tumour cells as well as in established cancer cell lines. Second, addition of 5-LO products to cultured tumour cells also led to increased cell proliferation and activation of anti-apoptotic signaling pathways. 5-LO antisense technology approaches demonstrated impaired tumour cell growth due to reduction of 5-LO expression. Lastly, pharmacological inhibition of 5-LO potently suppressed tumour cell growth by inducing cell cycle arrest and triggering cell death via the intrinsic apoptotic pathway. However, the documented strong cytotoxic off-target effects of 5-LO inhibitors, in combination with the relatively high concentrations of 5-LO products needed to achieve mitogenic effects in cell culture assays, raises concern over the assignment of the cause and question the relationship between 5-LO products and tumourigenesis.

【 授权许可】

Unknown